Previous studies have established that phorbol ester tumor promoters bind to and activate, protein kinase C (PK-C), suggesting a role for PK-C in transformation and tumor promotion. Current studies have been devoted to determining if PK-C activity is altered and regulated in cultured cells in response to growth factors and other hormones, as well as intransformed cells. In pinealocytes, there is a synergistic mechanism operative between aplha1- and beta-adrenergic agonists to elevate cyclic AMP levels. Treatment of pinealocytes with PMA, and with the synthetic diacylglycerol 1-oleoyl, 2-acetyl glycerol (OAG) (both of which act through stimulation of PK-C) was noted to mimic the effects of alpha-adrenergic agonists to enhance beta-adrenergic stimulation of pinealocyte cAMP accumulation. Further, treatment of these cells with the alpha1-aadrenergic agonist, phenylephrine, caused a rapid redistribution of PK-C activity from cytosol to pinealocyte membranes, indicating activation of this enzyme. These results suggest regulatory interaction between PK-C and neurotransmitter-dependent stimulation of cAMP levels. Exposure of an established lymphocyte cell line (CT6) to interleukin-2 (IL-2) was found to cause a rapid and transisent redistribution of PK-C activity from soluble to particulate fraction. Phorbol myristate acetate (PMA) treatment of CT6 cells induced a similar transposition of PK-C in an analogous manner with the exception that PMA-mediate PK-C transposition to the plasma membrane is not readily reversed. Other studies demonstrated that interleukin-3 treatment of FDC-P1 cells provoked a similar decrease in cytosolic PK-C activity concomitant with an increase in membrane-associated PK-C activity. Thus, changes in the activation and subcellular distribution of PK-C in response to growth factors, tumor promoters, and transformation factors, may play a critical role in regulating such cellular processes as cell growth, differentiation, and malignant transformation.